Efficacy and Safety of Org 25969 Administered After Zemuron® (MK-8616-042)

August 30, 2018 updated by: Merck Sharp & Dohme LLC

A Multi-center, Randomized, Assessor-blinded, Phase II, Parallel Dose-finding Trial in Subjects of ASA Class 1 - 3 to Assess the Efficacy and Safety of 5 Doses of Org 25969 When Administered at 1-2 PTCs After Administration of Zemuron®

The primary objective of this study is to explore the dose-response relation of MK-8616 (Org 25969) given as a reversal agent of Zemuron® at 1 to 2 post tetanic counts (PTCs); both Zemuron® and MK-8616 are administered by intravenous (iv) infusion. Another goal of the study is to evaluate the safety of single doses of MK-8616 administered to participants of American Society of Anesthesiologists (ASA) Physical Status Class 1 (otherwise normal, healthy participant); Class 2 (participant with a mild systemic disease); or Class 3 (participant with a severe systemic disease that limits activity, but is not incapacitating).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Has an ASA Class of 1 to 3
  • Is scheduled for surgical procedures (excluding dental and neck surgeries) with an anticipated duration of anesthesia of ≥45 minutes with the use of Zemuron®

Exclusion Criteria:

  • Is undergoing dental or neck surgery
  • Has anatomical malformation that would impede intubation
  • Has or is suspected to have neuromuscular disorders impairing neuromuscular block and/or significant renal dysfunction
  • Is known or suspected to have a family history of malignant hyperthermia
  • Is known or suspected to have an allergy to narcotics, muscle relaxants, or other medications used during general anesthesia
  • Is pregnant
  • Is a female of childbearing potential not using 1 of the following methods of birth control: condom or diaphragm with spermicide, vasectomized partner (<6 months), intrauterine device (IUD), or abstinence
  • Is breast-feeding
  • Has already participated in the study
  • Has participated in another clinical trial, not pre-approved by Organon Pharmaceuticals USA within 30 days of entering this study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 1) Zemuron® 0.6 mg/kg + MK-8616 0.5 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 0.5 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced neuromuscular blockade (NMB) reaches 1 to 2 PTCs.
Drug: MK-8616
MK-8616 will be administered at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg iv as a 30-second infusion. Doses are based on actual body weight.
Other Names:
  • Org 25969, sugammadex, Bridion®
Drug: Zemuron®
Zemuron® (0.6 or 1.2 mg/kg, iv) will be administered as a 10-second bolus infusion to achieve 1 to 2 PTCs. If needed, a maintenance dose of 0.15 mg/kg will be given. Doses are based on actual body weight.
Other Names:
  • Rocuronium bromide
EXPERIMENTAL: 2) Zemuron® 1.2 mg/kg + MK-8616 0.5 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 0.5 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
Drug: MK-8616
MK-8616 will be administered at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg iv as a 30-second infusion. Doses are based on actual body weight.
Other Names:
  • Org 25969, sugammadex, Bridion®
Drug: Zemuron®
Zemuron® (0.6 or 1.2 mg/kg, iv) will be administered as a 10-second bolus infusion to achieve 1 to 2 PTCs. If needed, a maintenance dose of 0.15 mg/kg will be given. Doses are based on actual body weight.
Other Names:
  • Rocuronium bromide
EXPERIMENTAL: 3) Zemuron® 0.6 mg/kg + MK-8616 1.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 1.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
Drug: MK-8616
MK-8616 will be administered at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg iv as a 30-second infusion. Doses are based on actual body weight.
Other Names:
  • Org 25969, sugammadex, Bridion®
Drug: Zemuron®
Zemuron® (0.6 or 1.2 mg/kg, iv) will be administered as a 10-second bolus infusion to achieve 1 to 2 PTCs. If needed, a maintenance dose of 0.15 mg/kg will be given. Doses are based on actual body weight.
Other Names:
  • Rocuronium bromide
EXPERIMENTAL: 4) Zemuron® 1.2 mg/kg + MK-8616 1.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 1.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
Drug: MK-8616
MK-8616 will be administered at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg iv as a 30-second infusion. Doses are based on actual body weight.
Other Names:
  • Org 25969, sugammadex, Bridion®
Drug: Zemuron®
Zemuron® (0.6 or 1.2 mg/kg, iv) will be administered as a 10-second bolus infusion to achieve 1 to 2 PTCs. If needed, a maintenance dose of 0.15 mg/kg will be given. Doses are based on actual body weight.
Other Names:
  • Rocuronium bromide
EXPERIMENTAL: 5) Zemuron® 0.6 mg/kg + MK-8616 2.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 2.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
Drug: MK-8616
MK-8616 will be administered at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg iv as a 30-second infusion. Doses are based on actual body weight.
Other Names:
  • Org 25969, sugammadex, Bridion®
Drug: Zemuron®
Zemuron® (0.6 or 1.2 mg/kg, iv) will be administered as a 10-second bolus infusion to achieve 1 to 2 PTCs. If needed, a maintenance dose of 0.15 mg/kg will be given. Doses are based on actual body weight.
Other Names:
  • Rocuronium bromide
EXPERIMENTAL: 6) Zemuron® 1.2 mg/kg + MK-8616 2.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 2.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
Drug: MK-8616
MK-8616 will be administered at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg iv as a 30-second infusion. Doses are based on actual body weight.
Other Names:
  • Org 25969, sugammadex, Bridion®
Drug: Zemuron®
Zemuron® (0.6 or 1.2 mg/kg, iv) will be administered as a 10-second bolus infusion to achieve 1 to 2 PTCs. If needed, a maintenance dose of 0.15 mg/kg will be given. Doses are based on actual body weight.
Other Names:
  • Rocuronium bromide
EXPERIMENTAL: 7) Zemuron® 0.6 mg/kg + MK-8616 4.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 4.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
Drug: MK-8616
MK-8616 will be administered at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg iv as a 30-second infusion. Doses are based on actual body weight.
Other Names:
  • Org 25969, sugammadex, Bridion®
Drug: Zemuron®
Zemuron® (0.6 or 1.2 mg/kg, iv) will be administered as a 10-second bolus infusion to achieve 1 to 2 PTCs. If needed, a maintenance dose of 0.15 mg/kg will be given. Doses are based on actual body weight.
Other Names:
  • Rocuronium bromide
EXPERIMENTAL: 8) Zemuron® 1.2 mg/kg + MK-8616 4.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 4.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
Drug: MK-8616
MK-8616 will be administered at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg iv as a 30-second infusion. Doses are based on actual body weight.
Other Names:
  • Org 25969, sugammadex, Bridion®
Drug: Zemuron®
Zemuron® (0.6 or 1.2 mg/kg, iv) will be administered as a 10-second bolus infusion to achieve 1 to 2 PTCs. If needed, a maintenance dose of 0.15 mg/kg will be given. Doses are based on actual body weight.
Other Names:
  • Rocuronium bromide
EXPERIMENTAL: 9) Zemuron® 0.6 mg/kg + MK-8616 8.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 8.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
Drug: MK-8616
MK-8616 will be administered at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg iv as a 30-second infusion. Doses are based on actual body weight.
Other Names:
  • Org 25969, sugammadex, Bridion®
Drug: Zemuron®
Zemuron® (0.6 or 1.2 mg/kg, iv) will be administered as a 10-second bolus infusion to achieve 1 to 2 PTCs. If needed, a maintenance dose of 0.15 mg/kg will be given. Doses are based on actual body weight.
Other Names:
  • Rocuronium bromide
EXPERIMENTAL: 10) Zemuron® 1.2 mg/kg + MK-8616 8.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 8.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
Drug: MK-8616
MK-8616 will be administered at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg iv as a 30-second infusion. Doses are based on actual body weight.
Other Names:
  • Org 25969, sugammadex, Bridion®
Drug: Zemuron®
Zemuron® (0.6 or 1.2 mg/kg, iv) will be administered as a 10-second bolus infusion to achieve 1 to 2 PTCs. If needed, a maintenance dose of 0.15 mg/kg will be given. Doses are based on actual body weight.
Other Names:
  • Rocuronium bromide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time From Start of Administration of MK-8616 to Recovery T4/T1 Ratio to 0.9
Time Frame: Up to 90 minutes
The mean time from the start of MK-8616 administration to recovery T4/T1 ratio of 0.9 was determined. Less time indicates faster recovery from NMB. The ratio of T4 (fourth twitch; amplitude of fourth response to train of four [TOF] stimulation is expressed as percent of control T4) over T1 (first twitch; amplitude of first response to TOF stimulation is expressed as percent of control T1) ranges from 0 (complete loss of T4 twitch response) to 1.0 (complete recovery of T4 twitch response). For TOF stimulation, 4 consecutive square wave supra-maximal stimuli of 0.2 msec duration were delivered at 2 Hz every 15 seconds. Neuromuscular monitoring was performed with the TOF-Watch® SX.
Up to 90 minutes

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Experiencing ≥1 Adverse Events (AEs)
Time Frame: Up to 7 days following MK-8616 administration
The percentage of participants experiencing ≥1 AEs was determined. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment.
Up to 7 days following MK-8616 administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

August 1, 2004

Primary Completion (ACTUAL)

May 26, 2005

Study Completion (ACTUAL)

May 26, 2005

Study Registration Dates

First Submitted

May 8, 2018

First Submitted That Met QC Criteria

May 8, 2018

First Posted (ACTUAL)

May 9, 2018

Study Record Updates

Last Update Posted (ACTUAL)

January 31, 2019

Last Update Submitted That Met QC Criteria

August 30, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P06387
  • MK-8616-042 (OTHER: Merck Protocol Number)
  • 19.4.204 (OTHER: Organon Protocol Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Neuromuscular Blockade

Clinical Trials on MK-8616

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Hong Kong

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe